AD Severity Research Articles

An update on the prevalence, chronicity, and severity of atopic dermatitis and the associated epidemiological risk factors in the Singapore/Malaysia Chinese young adult population: A detailed description of the Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort

BackgroundAtopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD. MethodsThere are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation. ResultsThe prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk. ConclusionsThese findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.

108 Recency bias in weekly POEM recording and its effects on POEM prediction

We recently developed a computational tool (EczemaPred) for personalised prediction of AD severity dynamics using PO-SCORAD. We aim to investigate whether EczemaPred can be applied to predict POEM score recorded weekly. We used data from 247 AD patients aged 11 to 65 years in a dose-finding study with up to 6 measurements of POEM and daily symptom scores for POEM over 16 weeks. We investigated the influence of the recency bias in reporting POEM by computing the partial cross-correlation between the observed POEM score and daily symptom scores recorded on the previous seven days using linear mixed-effects models.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms

Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

34679 Association of adult atopic dermatitis severity with decreased physical activity: A cross-sectional study

In multivariable logistic regression models controlling for age, sex, race/ethnicity and asthma history, patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), and Investigator’s Global Assessment (IGA) were associated with itch impairing light, moderate and vigorous physical activity, and higher Patient-Reported Outcome Measurement Information System Itch Questionnaire Physical Activity T-scores. Higher objective Scoring AD (O-SCORAD) was associated with itch impairing moderate physical activity. In bivariable analyses, odds of performing ≥30 minutes of light physical activity ≥1 day a week were lower with increased patient-reported AD severity, POEM, and EASI scores; ≥30 minutes of moderate physical activity ≥1 day a week were lower with increased patient-reported AD severity, EASI, O-SCORAD, and IGA; ≥30 minutes of vigorous physical activity were lower with increased patient-reported AD severity, EASI, O-SCORAD, and IGA scores. In multivariable logistic regression models, increased impact of itch on physical activity was associated with lower odds of performing light, moderate, and vigorous physical activity.

Burden of Atopic Dermatitis in Adults in Greece: Results from a Nationwide Survey.

The objective was to describe the AD burden in terms of quality of life (QoL), sleep, social life, work productivity, and resource utilization in Greece and assess the impact of disease severity. A nationwide cross-sectional survey was conducted. The questionnaire consisted of socioeconomic factors, medical history, AD screening, AD severity, QoL, sleep difficulties, social activities, and work productivity questions. AD was defined using the UK Working Party criteria (UKWP cohort) and a patient-reported AD diagnosis from a physician (Expert Diagnosis cohort). Self-reported moderate/severe AD was estimated using the Patient-Oriented Eczema Measure (POEM). In the UKWP cohort, the AD effect on QoL was moderate/extremely large in 84.3% of moderate/severe AD (vs. 55.7% in mild; p = 0.016), while in the Expert Diagnosis cohort, it was 72.2% (vs. 22.8%; p < 0.001). Disease severity was associated with a higher impact on sleep and social activities. Overall work impairment was high in both mild (32.7%) and moderate/severe (48.5%) AD of the UKWP cohort, while among the Expert Diagnosis cohort, it was significantly higher among those with moderate/severe (31.2%) versus mild AD (11.9%; p < 0.001). The AD burden in Greece is significant, especially for those in moderate/severe AD stages. Acknowledging this burden is the first step toward applying healthcare decisions that will benefit patients and the community.

Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial.

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of the pediatric population associated with alteration of skin and gut microbiome. Probiotics have been proposed for AD treatment. The ProPAD study aimed to investigate the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in children with AD.MethodsIn total, 100 AD patients aged 6–36 months were enrolled in a randomized, double‐blind, controlled trial to receive placebo (Group A) or LGG (1 x 1010 CFU/daily) (Group B) for 12 weeks. The primary outcome was the evaluation of the efficacy of LGG supplementation on AD severity comparing the Scoring Atopic Dermatitis (SCORAD) index at baseline (T0) and at 12‐week (T12). A reduction of ≥8.7 points on the SCORAD index was considered as minimum clinically important difference (MCID). The secondary outcomes were the SCORAD index evaluation at 4‐week (T16) after the end of LGG treatment, number of days without rescue medications, changes in Infant Dermatitis Quality Of Life questionnaire (IDQOL), gut microbiome structure and function, and skin microbiome structure.ResultsThe rate of subjects achieving MCID at T12 and at T16 was higher in Group B (p < .05), and remained higher at T16 (p < .05)The number of days without rescue medications was higher in Group B. IDQOL improved at T12 in the Group B (p < .05). A beneficial modulation of gut and skin microbiome was observed only in Group B patients.ConclusionsThe probiotic LGG could be useful as adjunctive therapy in pediatric AD. The beneficial effects on disease severity and quality of life paralleled with a beneficial modulation of gut and skin microbiome.

The Multidimensional Burden of Atopic Dermatitis Among Adults

Atopic dermatitis (AD) is long term and burdensome. Studies investigating disease burden in adults are limited in scope with gaps in understanding of the adult patient lived experience. To describe the multidimensional burden of AD among mainly US adults. This survey study for an externally led patient-focused drug development meeting with the US Food and Drug Administration on adult patients with AD was conducted between August 1, 2019, and October 11, 2019. Data were analyzed betwean March 26, 2021, and June 29, 2021. We used multivariable ordinal regression to assess associations between demographic and clinical variables and patient-reported overall AD impact scores (ordinal scale from 1 [no impact] to 5 [significant impact]). Among 1065 survey respondents, 114 (11%) were aged 18 to 24 years, 235 (22%) were 25 to 34 years, 242 (23%) were 35 to 50 years, 288 (27%) were 51 to 64 years, and 186 (17%) were aged 65 years or older; 881 (83%) were women. Four hundred eighty-nine (46%) participants reported low-moderate AD impact scores (2-3), 544 (51%) reported high-significant impact scores (4-5), whereas 32 (3%) reported no association of AD with disease burden (impact score, 1). Variables strongly associated with overall impact scores were current AD severity (moderate: OR, 4.13; 95% CI, 2.94-5.79; severe: OR, 13.63; 95% CI, 8.65-21.50 vs mild), and time spent managing AD (11-20 hours: OR, 2.67; 95% CI, 1.77-4.03, ≥21 hours: OR, 5.34; 95% CI, 3.22-8.85, vs <5 hours). In this survey study, AD severity and time spent managing symptoms showed the strongest associations with disease burden. This analysis highlights the multidimensional burden of AD in adults and emphasizes the need for more effective treatment strategies that reduce the time patients spend managing their AD.

Detecting Eczema Areas in Digital Images: An Impossible Task?

Assessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Those algorithms usually detect and then delineate (segment) AD lesions before assessing lesional severity and are trained using the data of AD areas detected by healthcare professionals. To evaluate the reliability of such data, we estimated the inter-rater reliability of AD segmentation in digital images. Four dermatologists independently segmented AD lesions in 80 digital images collected in a published clinical trial. We estimated the inter-rater reliability of the AD segmentation using the intraclass correlation coefficient at the pixel and the area levels for different resolutions of the images. The average intraclass correlation coefficient was 0.45 () corresponding to a poor agreement between raters, whereas the degree of agreement for AD segmentation varied from image to image. The AD segmentation in digital images is highly rater dependent even among dermatologists. Such limitations need to be taken into consideration when AD segmentation data are used to train machine learning algorithms that assess eczema severity.

EczemaPred: A computational framework for personalised prediction of eczema severity dynamics.

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease leading to substantial quality of life impairment with heterogeneous treatment responses. People with AD would benefit from personalised treatment strategies, whose design requires predicting how AD severity evolves for each individual.ObjectiveThis study aims to develop a computational framework for personalised prediction of AD severity dynamics.MethodsWe introduced EczemaPred, a computational framework to predict patient‐dependent dynamic evolution of AD severity using Bayesian state‐space models that describe latent dynamics of AD severity items and how they are measured. We used EczemaPred to predict the dynamic evolution of validated patient‐oriented scoring atopic dermatitis (PO‐SCORAD) by combining predictions from the models for the nine severity items of PO‐SCORAD (six intensity signs, extent of eczema, and two subjective symptoms). We validated this approach using longitudinal data from two independent studies: a published clinical study in which PO‐SCORAD was measured twice weekly for 347 AD patients over 17 weeks, and another one in which PO‐SCORAD was recorded daily by 16 AD patients for 12 weeks.ResultsEczemaPred achieved good performance for personalised predictions of PO‐SCORAD and its severity items daily to weekly. EczemaPred outperformed standard time‐series forecasting models such as a mixed effect autoregressive model. The uncertainty in predicting PO‐SCORAD was mainly attributed to that in predicting intensity signs (75% of the overall uncertainty).ConclusionsEczemaPred serves as a computational framework to make a personalised prediction of AD severity dynamics relevant to clinical practice. EczemaPred is available as an R package.

Can serum biomarkers predict the outcome of systemic immunosuppressive therapy in adult atopic dermatitis patients?

BackgroundAtopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification is of high clinical relevance, given a considerable variation in the clinical phenotype and responses to treatments among patients. It has been hypothesised that the measurement of biomarkers could help predict therapeutic responses for individual patients.ObjectiveWe aim to assess whether serum biomarkers can predict the outcome of systemic immunosuppressive therapy in adult AD patients.MethodsWe developed a statistical machine learning model using the data of an already published longitudinal study of 42 patients who received azathioprine or methotrexate for over 24 weeks. The data contained 26 serum cytokines and chemokines measured before the therapy. The model described the dynamic evolution of the latent disease severity and measurement errors to predict AD severity scores (Eczema Area and Severity Index, (o)SCORing of AD and Patient Oriented Eczema Measure) two‐weeks ahead. We conducted feature selection to identify the most important biomarkers for the prediction of AD severity scores.ResultsWe validated our model in a forward chaining setting and confirmed that it outperformed standard time‐series forecasting models. Adding biomarkers did not improve predictive performance.ConclusionsIn this study, biomarkers had a negligible and non‐significant effect for predicting the future AD severity scores and the outcome of the systemic therapy.

Quantitative systems pharmacology model of amyloid and tau to explore efficacy of therapy targeting modified forms of amyloid

AbstractBackgroundAmyloid targeting therapy in different variations is still under development. One of the potential targets is modified forms of amyloid, Ab3p. They are very specific marker found in plaques of AD subjects, and demonstrate higher toxicity to neurons. Its correlation with tau load and AD severity is stronger than for non‐modified forms. Specific therapy targeting modified Ab may be more effective and less toxic due to lower required concentration of antibodies. Glutaminyl cyclase (QC) inhibitors have considerable BBB penetration and concomitant anti‐inflammatory activities. Monoclonal antibodies to specific to pGlu3‐Ab successfully reduce cognitive impairment in preclinical settings. Quantitative systems pharmacology QSP model is a good tool to study contribution of protein modification to disease progression and investigating sensitivity of overall system to specific targeting.MethodQSP model was developed to describing amyloid production and distribution, hetero‐oligomerization of Ab1‐40, Ab1‐42 and pGlu3‐Ab. It has been combined with description of tau pathology and neuron homeostasis (NH) model. NH model describes processes regulating protein degradation and transport. Modified amyloid polymerizes with higher rate and resistant to degradation. Rate of amyloid modification was assumed to be one of the drivers, depending on age (we assumed it can be related to the calcium EPR stress in neurons and microglia activation due to inflammatory stimuli). Amyloid and tau during accumulation disrupt transport, proteasomal and autolysosome system. The model was calibrated on multiple in vitro and in vivo data, as well as preclinical and clinical data for treatments by immunotherapies.ResultIntegrated model describes accumulation of amyloid and tau according to Braak stages. It captures the role of intraneuronal processes on tau and amyloid metabolism. Model describes influence of amyloid modification on total accumulation of amyloid. Both QC inhibition and targeting by antibodies attenuate accumulation of amyloid in brain. Tau pathology progression is reduced, assuming that binding of antibody prevents toxicity of pGlu3‐Ab on tau kinase activation and calcium influx.ConclusionModel can be used to analyze contribution of different amyloid forms to pathology and efficacy of specific therapies on multiple biomarkers. It can be used for explorations of different combinations and regimens.

The effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe atopic dermatitis (ABC trial): study protocol for a pragmatic randomized controlled trial

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus (S.) aureus. Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD.MethodsThis is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed.DiscussionThis trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD.Trial registrationClinicalTrials.gov NCT04297215. Registered on 5 March 2020

The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment.

BackgroundAtopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics.ObjectivesTo characterize changes in the skin microbiome during treatment for AD.MethodsThe skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification.ResultsWe included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment.ConclusionsThere are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

PIH36 How Does Caregiver Burden Change As Alzheimer's Dementia (AD) Severity Advances?

While the progression of caregiver burden is thought to increase as AD severity worsens, the literature on this topic has not been summarized. Caregiving accounts for the highest cost associated with AD management, in the absence of any disease modifying treatments. A well-characterized trajectory of caregiver burden across AD severity would allow value demonstration of future AD treatment options that might delay disease progression. To compile and summarize published studies reporting AD caregiver burden in an effort to profile the change in caregiver burden with AD progression. A systematic literature search was conducted using PubMed and EMBASE for articles published from 2004 to 2020. Randomized controlled trials and observational studies assessing dyads of patients with AD and their caregivers were included. Caregiver burden quantified via the Zarit Burden Interview (ZBI) Scale, a 22-item scale that is predominantly used and well-validated to assess caregiver burden, was then grouped according to AD severity. Articles lacking AD severity data, articles with non-unique samples, and non-English studies were excluded. Of 167 studies found, 152 full-text articles were screened after duplicates were removed, and 18 studies met the inclusion and exclusion criteria. Overall, the compiled data supports the notion that caregiver burden increases with worsening AD. However, the degree of change appears to vary depending on factors such as country, caregiver relationship to the patient, and caregiver gender. The paucity of caregiver burden data available in the United States emphasizes the need for further studies elucidating caregiver burden progression in the United States. A better understanding of the course of caregiver burden would permit future cost-effectiveness studies and economic modeling of AD treatment options to demonstrate value for products that might delay disease progression and in turn reduce caregiver burden

Assessing patients\u2019 characteristics and treatment patterns among children with atopic dermatitis

BackgroundAtopic dermatitis (AD) is the most common immune-mediated skin disease in childhood. Several treatment options for pediatric AD, both topical and systemic, are currently available. We carried out a single-center observational study with the aim of describing characteristics and treatment patterns in pediatric AD patients.MethodsThe study included 867 patients aged ≤16 years (females 50.5%, mean patient’s age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AD who underwent balneotherapy at the Comano Thermal Spring Water Center (Comano, Trentino, Italy) from April to October 2014.ResultsAmong the patients included in the study, 41.2% had mild (SCORing Atopic Dermatitis, SCORAD 0-15), 43.6% moderate (SCORAD 16–40) and 15.2% severe AD (SCORAD > 40). A higher occurrence of reported food allergy was observed among children with more severe AD (p < 0.0001), while no association was found between AD severity and reported inhalant allergy or passive smoking (p = 0.15 and 0.92, respectively). Emollients (55.1%) and topical corticosteroids (TCS; 45.7%) were the main treatment options used in the previous month. The use of oral steroids and topical calcineurin inhibitors (TCI) was considerably less common (6.3 and 4.5%, respectively), while no patients were on systemic agents other than steroids. Among patients with severe AD, 9.8% had not used TCS, TCI or any systemic treatments. Moreover, 20.0% of the patients in the study population had followed elimination diets, although only 27.2% of them had a reported food allergy.ConclusionsA significant difference in the prevalence of reported food allergy emerged across the different AD severity categories. Furthermore, although further data are necessary to confirm our findings, undertreatment in children with AD appeared to be very common, at least among those attending the Comano Thermal Spring Water Center. Moreover, many patients followed elimination diets in the absence of reported food allergy.

Topical corticosteroids normalize both skin and systemic inflammatory markers in infant atopic dermatitis.

SummaryBackgroundAtopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood.AimsWe used noninvasive skin and peripheral biomarkers to observe the effects of real‐world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy.MethodsSeventy‐four treatment‐naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls.ResultsTCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)‐18, IL‐8 and IL‐1α, and the Th2 chemokines C‐C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2‐skewed biomarkers: CCL17, IL‐13, CCL22, IL‐5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF.ConclusionsThe profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long‐term beneficial effects of correcting systemic immune dysregulation through topical therapy.

Validity and reliability of a novel numeric rating scale to measure skin-pain in adults with atopic dermatitis.

Little is known about the measurement properties of numeric rating scales (NRS) for pain in AD. We evaluated a novel NRS for skin-pain and existing NRS for average overall-pain in adults with AD. Self-administered questionnaires and skin-examination were performed in 463 AD patients (age 18-97years) in a dermatology practice setting. Numeric rating scales skin-pain and average overall-pain had moderate correlations with each other, and multiple clinician-reported and patient-reported AD severity outcomes (Spearman correlations, P < 0.0001). There were significant and stepwise increases of NRS skin-pain and average overall-pain scores with patient-reported global severity (Wilcoxon rank-sum test, P < 0.0001). Floor-effects were observed for NRS skin-pain and average overall-pain. Changes from baseline in NRS skin-pain and average overall-pain showed weak-moderate correlations with changes of POEM, vIGA-AD*BSA, SCORAD, and DLQI. Using an anchoring approach, the optimal interpretability band for NRS skin-pain was clear = 0, mild = 1-3, moderate = 5-6, severe = 7-9, and very severe = 10 (weighted kappa = 0.4923). The thresholds for minimally clinically important difference for NRS skin-pain ranged from 2.2 to 2.9. NRS skin-pain and average overall-pain showed moderate-good reliability. Numeric rating scales skin-pain and average overall-pain had sufficient validity, reliability, responsiveness, and interpretability in adults with AD, and were inherently feasible as single-items for use in clinical trials and practice.

Assessment of the Psychological Burden Among Family Caregivers of People Living with Alzheimer's Disease Using the Zarit Burden Interview.

In China, family caregivers play a major role in caring for people living with Alzheimer's disease (PLWAD), but little is known about the burden this creates. This study aimed to investigate the burden among family caregivers of PLWAD and the factors influenced it. Family caregivers of PLWAD were recruited from a hospital in China from January 2018 to July 2018. All data were collected online using the Chinese version of the Zarit Burden Interview (ZBI), and the participants' sociodemographic and caregiving details were obtained. T-tests and Kruskal-Wallis H (K) tests were used to compare ZBI scores between groups. Factors related to the caregiver psychological burden were analyzed using multiple linear regression analysis. A total of 300 participants were assessed, of which 213 (71.00%) were female. More than half of the caregivers were the patient's daughter (51.0%, n = 153). The average ZBI score of the caregivers was 43.05 (13.42). The level of burden was influenced by age, the relationship of the caregiver to the patient, the severity of AD, the caregiver's retirement status, the income level of the caregiver, and the caring time. Regression analysis showed that retired caregivers were more likely to have higher levels of burden and that burden increased with AD severity. Most family caregivers of PLWAD have a considerable caregiver psychological burden. The findings increase the understanding of factors that influence family caregiver burden, and pave the way for potential interventions, such as social support and caregiver empowerment, to reduce their burden.

Combination of FLG mutations and SNP of TSLP (rs1898671) influence on atopic dermatitis occurrence.

IntroductionAtopic dermatitis (AD) is a common, chronic, relapsing and heterogeneous inflammatory skin disease. Its main causes are genetic predispositions, the epidermal barrier defect, and immune system dysfunction. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of AD patients and its production is triggered by exposure to environmental factors, allergens, microorganisms and irritants.AimTo search for the associations between rs1898671 polymorphism in the promotor region of the TSLP gene (SNP) and AD occurrence and course.Material and methodsThe frequency of polymorphism occurrence was examined, connection with IgE level, the severity of AD, itching, and concomitant asthma occurrence and combination with FLG gene mutations (2282del4, R501X) in the population of northern Poland. Blood samples were collected from 239 patients with AD and 170 controls. SNP of TSLP and FLG null mutations were analysed. PCR and RFLP restriction fragment length polymorphism analysis was used.ResultsNo polymorphisms of studied cytokines caused more frequent occurrence of AD compared to controls. We found no associations between TSLP gene polymorphism and AD severity (p = 0.395), IgE level (p = 0.895), VAS (p = 0.918) or concomitant asthma (p = 0.742).ConclusionsThe SNP of TSLP rs1898671 does not influence the AD course and occurrence. 2282del4 FLG mutation is a key influencer in AD. However, the coexistence of FLG mutations and SNP of TSLP may play a protective role.

Vitamin B12 and Atopic Dermatitis: Any Therapeutic Relevance For Oral Supplementation?

In vitro experimental studies have demonstrated the anti-inflammatory and immune-regulatory potential of vitamin B 12. Nevertheless, few studies have explored so far the relevance of topical products containing vitamin B12 as a treatment option for atopic dermatitis, and the association between blood levels of Vitamin B12 and the severity of atopic dermatitis has never been investigated. Thus the effect of Vitamin B12 oral supplementation in atopic dermatitis is unknown. We describe the case of a 18 years old boy affected by severe refractory atopic dermatitis requiring continuous topical steroid therapy and 5-6 oral steroid trials per year to achieve satisfactory control. During a three years follow-up, an association between Vitamin B12 blood levels and atopic dermatitis severity was detected, as well as a clinically significant SCORAD improvement following Vitamin B12 oral supplementation. Although the cause-effect relationship between Vitamin B12 deficiency and AD severity or relapse needs to be confirmed in larger studies, our case report suggests that Vitamin B12 levels deserve to be assessed in patients with difficult to control atopic dermatitis and points out the potential therapeutic relevance of Vitamin B12 oral supplementation.